1. Technical Field
The present disclosure relates to compositions and methods for quantitatively amplifying nucleic acid molecules from biological samples and, more particularly, to a panel of nucleic acid molecules useful for quantitative amplification of target markers for detecting, diagnosing, or monitoring individuals who have or are at risk of certain disease conditions, such as autoimmune disease, proliferative disease, infectious disease, allograft rejection, or pregnancy-related pathologies.
2. Description of Related Art
Individuals harbor small amounts of foreign cells or DNA, referred to as microchimerism (“Mc”). Acquisition of Mc occurs naturally during pregnancy primarily through transplacental cell trafficking between mother and fetus, although Mc may be acquired through other sources (e.g., twin-twin transfer, possibly from older sibling, blood transfusion, organ transplantation). An adult woman may have acquired Mc from her own mother (maternal Mc, “MMc”) while she herself was a fetus. This “graft,” acquired during fetal immune system development, can remain in her system into adulthood (Maloney et al., J. Clin. Invest. 104:41, 1999; Lambert et al., Arth. Rheu. 50:906, 2004) and represents a pre-existing inhabitant as she experiences pregnancy herself. During subsequent pregnancies, new fetal sources of microchimerism (fetal Mc, “FMc”) can be acquired and also remain for years. The interactions of each of these grafts with the host, and with other pre-existing inhabitants, may be beneficial or detrimental to an individual.
Disease and Mc may have a functional connection since persistence of Mc has been shown to be associated both positively and negatively with certain disease states, such as autoimmune disease (Evans et al., Blood 93:2033, 1999; Yan et al., Arth. Rheu. 63:640, 2011), malignancy (Gadi, Breast Cancer Res. Treat. 121:241, 2010; Gadi et al., PLoS ONE 3:e1706, 2008), and transplant rejection (Gadi et al., Clin. Chem. 52:379, 2006; Gadi et al., Transpl. 92:607, 2011). In autoimmunity, higher detection rates and concentrations of Mc suggest a possible allo-autoimmune or auto-alloimmune functionality (Gammill and Nelson, Int. J. Dev. Biol. 54:531, 2010). In the case of malignancy, lower detection rates and concentrations of Mc in cancer cases suggest a possible graft-versus-tumor effect (Gadi, Cancer Lett. 276:8, 2009). In transplantation, the presence of Mc may serve as a biomarker for monitoring allograft survival (Gadi et al., 2006, 2011).
From the foregoing, a need is apparent for improved compositions and methods for sensitively and quantitatively identifying allogeneic cells, tissues, and nucleic acids resulting from medical conditions or interventions.